PTEN inhibitors for treatment and prevention of bone marrow loss

Abstract

The present disclosure relates to pharmaceutical compositions comprising PTEN inhibitors and methods of treating or preventing bone marrow loss in subjects in subjects in need thereof. The compositions and methods of this disclosure are useful in treating or preventing bone marrow loss associated with exposure to nuclear radiation or chemotherapeutic treatment.

What is claimed: 
     
       1. A method of ameliorating a disease, disorder, syndrome, or condition amenable to amelioration by a PTEN inhibitor in a subject in need thereof, wherein the disease, disorder, syndrome, or condition is acute radiation syndrome, comprising administering to the subject an effective amount of a PTEN inhibitor selected from the group consisting of:
 verteporfin or a pharmaceutically acceptable salt thereof; 
 candicidin or a pharmaceutically acceptable salt thereof; 
 cyanocobalamin or a pharmaceutically acceptable salt thereof, 
 1-palmitoyl-2-oleoyl-sn-glycero-3-(phospho-rac-(1-glycerol)) or a pharmaceutically acceptable salt thereof; 
 fondaparinux or a pharmaceutically acceptable salt thereof; 
 trypan blue free acid or a pharmaceutically acceptable salt thereof; 
 indocyanine green acid form or a pharmaceutically acceptable salt thereof; 
 DL-dimyristoylphosphatidylglycerol or a pharmaceutically acceptable salt thereof; and 
 tannic acid or a pharmaceutically acceptable salt thereof. 
 
     
     
       2. The method of  claim 1 , comprising administering to the subject an effective amount of a PTEN inhibitor wherein amelioration of the disease, disorder, syndrome, or condition requires regenerating bone marrow. 
     
     
       3. The method of  claim 2 , wherein the subject experiences bone marrow loss as a result of exposure to nuclear radiation. 
     
     
       4. The method of  claim 1 , comprising administering to the subject an effective amount of a PTEN inhibitor wherein amelioration of the disease, disorder, syndrome, or condition requires ameliorating exposure to nuclear radiation. 
     
     
       5. The method of  claim 4 , wherein the PTEN inhibitor is administered in an amount effective to reduce apoptosis, bone marrow loss, damage to the gastrointestinal epithelium, or an increased risk of infection in the subject caused by exposure to nuclear radiation. 
     
     
       6. The method of  claim 4 , wherein the PTEN inhibitor is administered about 1 hour to about 2 weeks after exposure to nuclear radiation. 
     
     
       7. The method of  claim 1 , comprising administering to the subject an effective amount of a PTEN inhibitor wherein amelioration of the disease, disorder, syndrome, or condition reduces the likelihood of Acute Radiation Syndrome. 
     
     
       8. The method of  claim 7 , wherein the PTEN inhibitor is administered during exposure to nuclear radiation. 
     
     
       9. The method of  claim 1 , wherein a pharmaceutical composition comprises the PTEN inhibitor. 
     
     
       10. The method of  claim 9 , wherein the pharmaceutical composition is a solid dosage form, or a tablet or capsule. 
     
     
       11. The method of  claim 9 , wherein the pharmaceutical composition is for oral, parenteral, intravenous, intramuscular, or subcutaneous administration. 
     
     
       12. The method of  claim 1 , wherein the subject is a human. 
     
     
       13. The method of  claim 1 , wherein administration of an amount of the PTEN inhibitor is as effective or more effective in activating NFκB in the subject as administration of an equimolar amount of a flagellin protein purified from  Salmonella enterica.